The present invention relates to a new compound, designated B-41D, which can be prepared by the cultivation of microorganisms of the genus Streptomyces and which has valuable acaricidal and anthelmintic activities.
We have disclosed in our British Patent Specification No. 1,390,336 that microorganisms of the genus Streptomyces, and especially Streptomyces strain B-41-146 (Ferm 1438), can produce an antibiotic substance B-41, which can be separated into 9 different constituents, which are designated in that Specification as A.sub.1, A.sub.2, A.sub.3, A.sub.4 B.sub.1, B.sub.2, B.sub.3, C.sub.1 and C.sub.2. Subsequently, it was discovered that four other compounds of similar structure could be obtained by cultivating the same strain of Streptomyces. The structure and properties of all thirteen compounds are described, inter alia, in J. Antibiotics 29 (3), pages 76-14 to 76-16 and 29 (6), pages 76-35 to 76-42.
Subsequently, a series of compounds structurally similar to the compounds making up substance B-41 were discovered and named the "avermectins" (or "C-076"). The avermectins and derivatives thereof are disclosed in: U.S. Patent Application Ser. No. 678,328; Antimicrobial Agents and Chemotherapy, 15 No. 3, pages 361-367 (1979), U.S. Pat. No. 4,206,205, European Patent Application No. 0,001,689; U.S. Pat. No. 4,171,314; U.S. Pat. No. 4,173,571; European Patent Application No. 0,002,615; and European Patent Application No. 0,008,184.
In British Pat. No. 1,390,336, it was disclosed that the complex of substances B-41 together and individually had insecticidal and acaricidal properties. Subsequently, in U.S. Pat. No. 4,144,352, it was disclosed that these and related substances also had anthelmintic activity. In U.S. Pat. No. 4,144,352, the B-41 substances were referred to as "milbemycins". For clarity, we, too, in this Specification refer to the prior art compound as "milbemycins", although it will be appreciated that certain of these compounds are identical to those compounds making up substance B-41, as described in British Patent Specification No. 1,390,336. Various milbemycin derivatives are disclosed in U.S. Pat. No. 4,093,629 and No. 4,134,973.
The thirteen milbemycin compounds which can be produced by cultivation of Streptomyces B-41-146 have the formulae (I), (II) and (III). the structure of milbemycins .alpha..sub.1-10 is given by formula (I): ##STR2## The definitions of the groups R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are given in the following Table 1, which also shows, where appropriate, the corresponding B-41 designation, as used in British Patent Specification No. 1,390,336. Of the thirteen known compounds produced by Streptomyces strain B-41-146, the milbemycins .alpha..sub.1-10 are closest in structure to the new Compound B-41D of the present invention and the appropriate definitions of the groups R.sup.1 -R.sup.5 as applied to Compound B-41D are also given in Table 1.
In this Table, the following abbreviations are used:
MH means a 2-methylhexanoyloxy group of formula ##STR3##
PC means a 2-pyrrolylcarbonyloxymethyl group of formula ##STR4##
TABLE 1 ______________________________________ Milbemycin R.sup.1 R.sup.2 R.sup.3 R.sup.4 R.sup.5 B-41 ______________________________________ .alpha..sub.1 H H CH.sub.3 CH.sub.3 OH A.sub.3 .alpha..sub.2 H H CH.sub.3 CH.sub.3 OCH.sub.3 B.sub.2 .alpha..sub.3 H H C.sub.2 H.sub.5 CH.sub.3 OH A.sub.4 .alpha..sub.4 H H C.sub.2 H.sub.5 CH.sub.3 OCH.sub.3 B.sub.3 .alpha..sub.5 OH MH CH.sub.3 CH.sub.3 OH A.sub.2 .alpha..sub.6 OH MH CH.sub.3 CH.sub.3 OCH.sub.3 B.sub.1 .alpha..sub.7 OH MH C.sub.2 H.sub.5 CH.sub.3 OH -- .alpha..sub.8 OH MH C.sub.2 H.sub.5 CH.sub.3 OCH.sub.3 -- .alpha.9 H H CH.sub.3 PC OH C.sub.1 .alpha..sub.10 H H C.sub.2 H.sub.5 PC OH C.sub.2 -- H H CH(CH.sub.3).sub.2 CH.sub.3 OH D ______________________________________
The structures of milbemycins .beta..sub.1 and .beta..sub.2 are given in formula (II): ##STR5## in which R.sup.6 represents, for milbemycin .beta..sub.1, a methyl group and, for milbemycin .beta..sub.2, an ethyl group. Milbemycin .beta..sub.1 corresponds to Compound B-41A.sub.1 of British Patent Specification No. 1,390,336.
The structure, of milbemycin .beta..sub.3 is given by formula (III): ##STR6##